Evaluation of a New Oxytocin Protocol

Lauren Healy, PharmDPharmacy Practice Resident

Northwestern Memorial HospitalChicago, IL

The speaker has no conflict to disclose.

Learning Objectives• Review the use of oxytocin in labor and

delivery (L+D)• Review the potential advantages of

implementing a standardized oxytocin protocol

• Discuss the effect of an oxytocin infusion protocol that includes active management of the 3rd stage of labor on hypotension in cesarean deliveries

Oxytocin• Endogenous oxytocin is a hormone secreted by

the hypothalamus and stored in the posterior pituitary

• It stimulates contraction of uterine smooth muscle during gestation and causes milk ejection after milk has been produced in the breast

• Clinically, oxytocin is commonly used to induce/augment labor and control postpartum bleeding associated with third stage of labor

Oxytocin. Clinical Pharmacology [database online]. Available at: http://www.clinicalpharmacology.com. Accessed: April 16, 2009.Pitocin ® [package insert]. Rochester (MI): JHP Pharmaceuticals; 2007.

Third Stage of Labor• Time from birth of the baby to delivery of

the placenta• On average lasts about 5-6 minutes• The most important complication of the

third stage of labor is post partum hemorrhage (PPH)

Prendiville WJP. The Cochrane Library 2008, Issue 4.Dombrowski MP. J Obstet Gynecol 1995 Apr;172(4 Pt 1):1279-84.Combs CA. Obstet Gynecol 1991 Jun;77(6):863-7.

Post Partum Hemorrhage• PPH is an obstetric emergency that can follow

vaginal or cesarean deliveries• Incidence of PPH varies, but it is estimated to

occur in 1-5% of deliveries• PPH is one of the top five causes of maternal

mortality• PPH in vaginal delivery

– Maternal blood loss of >500 mL• PPH in cesarean delivery

– Maternal blood loss of >1000 mL

Prendiville WJP. The Cochrane Library 2008, Issue 4.Mousa HA. Cochrane Database Syst Rev 2003;(1).

Post Partum Hemorrhage• Treatment – Uterotonics or “Rescue

Medications”– Methylergonovine

• 0.2 mg IM– Carboprost Tromethamine

• 250 mcg IM– Misoprostol

• 800-1000 mcg rectally• 200 mcg PO + 400 mcg sublingually • 200 mcg PO + 400 mcg sublingually + 400 mcg rectally

Methergine® [package insert]. East Hanover (NJ): Novartis; 2006.Hemabate® [package insert]. New York (NY): Pfizer; 2006.Cytotec ® [package insert]. New York, (NY): Pfizer; 2006.

Management of Third Stage of Labor

• Expectant management (conservative or physiological management)– Spontaneous delivery of placenta

• Active management– Administration of prophylactic oxytocin with or

directly after delivery of the baby– Early cord clamping and cutting– Controlled traction of the umbilical cord– Standard practice in UK, and Australia

Prendiville WJP et al. The Cochrane Library 2008, Issue 4.Chong YS. Curr Opin Obstet Gynecol 16:143–150

Management of Third Stage of Labor• 5 randomized controlled trials of active versus

expectant management of third stage of labor• In maternity units in Ireland or UK• Used oxytocin, ergometrine, or a mixture

(Syntometrine-not available in US)• Trials

– Abu Dhabi. Am J Obstet Gynecol 1997;177:770-4.– Brighton. Eur J Obstet Gynecol Reprod Biol 1993;48:19-

22.– Bristol. BMJ 1988;297:1295-300.– Dublin. Midwifery 1990;6:60-72.– Hichingbrooke. Lancet 1998;351:693-9.

Prendiville WJP et al. The Cochrane Library 2008, Issue 4

Management of Third Stage of Labor

Prendiville WJP et al. The Cochrane Library 2008, Issue 4.

Active Expectant

Odds Ratio

Potential Adverse Effects of Oxytocin• Pinder, AJ. Int J Obstet Anesth (2002) 11,

156-9.– Prospective, randomized, double blind– 34 healthy term parturients for cesarean section (CS)

under spinal anesthesia– Rapid IV bolus of 5 or 10 units of oxytocin was

administered upon delivery of the infant– Reduction in MAP 30 seconds after 10 unit infusion

(P<0.05)– Increased HR and CO 1 minute after 5 unit infusion

and 2 minutes after 10 unit infusion (P<0.05)

Potential Adverse Effects of Oxytocin

• Svanstrom, MC. Br J Anaesth 2008;100:683-9.– Prospective, randomized, double blind– 40 women undergoing elective CS under spinal

anesthesia– IV bolus of 10 units oxytocin or 0.2 mg

methylergometrine– Control group of 10 non-pregnant, non-anesthesized

women were given 10 units oxytocin IV– Oxytocin produced significant increase in HR

(P>0.001), decrease in MAP (P<0.001), and ECG changes (P<0.001) in CS patients and controls

Why a New Protocol?• Compared to expectant management,

active management of third stage of labor was associated with reduced risk of PPH

• Oxytocin given at or above certain amounts, can cause undesired hemodynamic changes during cesarean delivery

Su LL. Cochrane Database Syst Rev. 2007; 18;(3).Prendiville WJ. Cochrane Database Syst Rev. 2000; (3).Elbourne DR. Cochrane Database Syst Rev. 2001; (4).Chong YS. Curr Opin Obstet Gynecol. 2004; 16(2): 143-50.Svanström MC. Br J Anaesthesia 2008; 100(5): 683-9.Pinder AJ. Int J Obstet Anesthesia 2002; 11(3): 156-9.

Time for a Change• On November 17, 2008, a multidisciplinary

team implemented a new protocol at Prentice Women’s Hospital for the administration of oxytocin post-delivery (vaginal and cesarean)

Prentice Women’s Hospital

• Part of Northwestern Memorial Hospital– Large academic

medical center in Chicago, IL

• Largest birthing center in the Midwest

• 11,675 deliveries in 2008

New ProtocolBEFORE AFTER

Concentration available

15 units/250 mL NS10 units/500 mL NS

30 units/500 mL NS

Rate of Infusion

Often “wide open” or “off the pump”

18 units over 1 hour* then 3.6 units/hour

When started After delivery of the placenta (expectant)

After delivery of the fetus (active)

*Could be increased to 36 units in the presence of uterine atony

Potential Advantages • Efficacy

– Facilitates active management of third stage of labor

• Safety– A single concentration of oxytocin on L+D

floors– Consistent practice– Fewer adverse events

• Cost– Cost and space savings

Study Objectives• Assess protocol compliance and cost

savings• Assess the effect of this new protocol on

EBL, and use of rescue medications• Determine the effect of this new protocol

on the incidence of hypotension as defined by use of vasopressors in cesarean deliveries

Methods• Retrospective Chart Review• Inclusion Criteria

– Patients receiving neuraxial analgesia surrounding protocol implementation

– Before: 9/15/08 – 11/15/08– After: 11/20/08 – 1/09/09

• Exclusion Criteria– Receipt of general anesthesia for a cesarean

delivery

Data Collection• Patient Demographics

– Age– Gravity/Parity status

• Delivery type• Amount of oxytocin infused following delivery• Estimated blood loss (EBL)• Administration of rescue medications• # of hypotensive episodes requiring vasopressor

administration

Statistical Analysis• Data was stratified by the delivery type

and compared between before and after protocol implementation

• Descriptive statistics were used to analyze continuous data

• Mann Whitney U test was used to compare independent groupsα = 0.05

Results

Protocol ComplianceProtocol Implementation

0

500

1000

1500

2000

2500

3000

Sep-08 Oct-08 Nov-08 Dec-08 Jan-09Month

# O

xyto

cin

bags

pur

chas

ed

10 IU/500 mL

15 IU/250 mL

30 IU/500 mL

Protocol Compliance

0123456789

10

Before After

Time

# ru

n at

999

mL/

hour

Cost Savings• FY ’09 2nd quarter (12/08 – 2/09)

– Oxytocin delivery protocol fully implemented– Savings = $17,666

• Projected annualized savings– $70,664

Baseline CharacteristicsVaginal Delivery Cesarean Delivery

Before After p Before After p

n 601 472 - 361 381 -

Age 31.5+5.3 31.3+5.4 0.608 32.4+5.9 32.6+5.7 0.385

Amount oxytocin infused (units)

13.5+6.3 22.4+7.7 0 22+8.1 14+8 0

Gravity 2.3+2.3 2.2+1.4 0.648 2.1+1.3 2.2+1.4 0.405

Parity 0.71+1.0 0.69+1.0 0.717 0.66+0.88 0.6+0.83 0.388

Values are shown as mean + standard deviation

Estimated Blood LossEstimated blood loss (mL)

Vaginal Delivery

Before 355 + 356

After 323 + 106

p 0.43

Cesarean Delivery

Before 789 + 318

After 846 + 283

p 0.003

Values are shown as mean + standard deviation.

Rescue Medication Use

0

10

20

30

40

50

60

Vaginal Delivery C es areanDelivery

Total

Delivery type

# of patients that rec

eive

d res

cue 

med

ications

Before P rotocol

After P rotocol

P=0.647P=0.474

Episodes of Hypotension

178 189

0

50

100

150

200

Before AfterTime

# H

ypot

ensi

ve E

piso

des

P = 0.417

Conclusions• Based on purchase data and smart pump

usage data, the L+D teams have been compliant with the protocol

• This new protocol will provide an annual cost savings of over $70,500

Conclusions• There was no statistically significant change in

EBL for vaginal deliveries, and an increased EBL of 50mL found for cesarean deliveries

• The amount of rescue medications used did not change for either group surrounding protocol implementation

• The number of hypotensive episodes in cesarean deliveries is not statistically significantly different surrounding protocol implementation

Implications• Implementation of a protocol standardizing

oxytocin administration is beneficial in terms of usage and cost and did not confer significant increase in rate of adverse events such as hypotension

Limitations• Retrospective review• Paper chart review• Restricted time frame

Resident’s Role• Study design• Chart review and data collection

– Recruiting, training, and overseeing pharmacy students in data collection

• Statistical Analysis• Data Interpretation

Future • Protocol will continue• Data will be presented at OB Quality and

Safety committee meeting and P+T meeting

• Further data collection• Re-analyze data to see if outcomes

change as protocol is in place longer • Manuscript preparation

Acknowledgements• Cynthia A. Wong, MD• Amy Lee, MD• Paloma Toledo, MD• Soha Elsamadoury, PharmD Candidate• Robert McCarthy, PharmD• Despina Kotis, PharmD• Joslyn Emerson, PharmD• Noelle Chapman, PharmD, BCPS• Mike Postelnick, BSPharm, BCPS• Michael Fotis, BSPharm

Lauren Healy, PharmD Evaluation of a New Oxytocin Protocol

Post-Test Questions

1. TRUE or FASE? MR is a 31 y/o woman who gives birth vaginally, but loses an estimated 1200mL of blood in the process. She would be a candidate for administration of Carboprost Tromethamine.

2. Which of the following are potential adverse effects of administering oxytocin

“off the pump” or “wide open”? A. Hypotension B. Chest Pain C. Tachycardia D. ECG Changes E. All of the above

Anticholinergic Use in Children and Adolescents

Taking Antipsychotics

Irene Hong, Pharm.D.PGY2 Resident – Drug Information

September 12, 2009

No conflict of interest to disclose

Objectives• Review the use of antipsychotics in

children and adolescents• Compare anticholinergic use across

children and adolescents receiving aripiprazole, risperidone, and quetiapine

Antipsychotics• Two second generation antipsychotics (SGA)

approved for use in pediatric patients: – Aripiprazole, Risperidone

• Both approved for:– Schizophrenia (13 y/o)– Bipolar type I (10 y/o)

• Risperidone also for:– Irritability associated with autism (5 y/o)

Antipsychotics• All target dopamine type-2 receptors (D2)• First Generation Antipsychotics (FGA): Bind

more tightly, dissociate more slowly• SGA: Bind more loosely, dissociate more

rapidly– Also block serotonin type-2A receptors,

reducing side-effect liability of D2 receptor antagonists

Antipsychotics• Clinical observations indicate

children/adolescents may be more sensitive• In a review of the use of risperidone in youth

with bipolar disorder and schizophrenia, EPS reported in up to 61.5% of subjects – Higher percentages (up to 67%) of anticholinergic

use in patients receiving risperidone ≥ 3.3 mg daily

Bishop JR. Neuropsychiatr Dis Treat. 2008;4(1):55-68.

EPS

DA ACh

DA

ACh

Antipsychotic Absent:

Antipsychotic Present:

DA = dopamineACh = acetylcholine

Anticholinergics• Restore balance of

dopaminergic/cholinergic activity• Examples: benztropine, diphenhydramine,

trihexyphenidyl

DA ACh

Anticholinergic Risks vs Benefits

Benefits• Treat EPS

– EPS may be stigmatizing

– Affects social interactions

– May disrupt learning • Fine motor skills

(writing)• Restlessness

Risks• May cause sedation,

cognitive dulling, memory impairment

• Worsening performance in school

• Other side effects

Which of the following antipsychotic medications is most likely to requirethe use of anticholinergic therapy to control or prevent EPS in a 15 year old patient with schizophrenia?

A. QuetiapineB. AripiprazoleC. RisperidoneD. All of the above

Study Purpose• To characterize proportion of patients 5 to

18 y/o taking antipsychotics at UIC• To identify clinical characteristics

associated with anticholinergic use in children and adolescents

• To compare anticholinergic use across pediatric patients receiving aripiprazole, risperidone, and quetiapine

Study Design• Retrospective chart review• Subjects identified through UIC outpatient

pharmacy prescription database– Prescription for antipsychotics filled between

January 1, 2005 and September 1, 2008

Approved by UIC investigational review board

Study Design

Inclusion Criteria• Age: 5 to 18 y/o• Received at least 2

consecutive months of SGA◦ 2 consecutive refills in

pharmacy database◦ Presence of medication

in electronic medical record notes from visits spanning ≥60 days

Exclusion Criteria• Age: ≥19 y/o• Medication other than

antipsychotic causing EPS

• Neurologic disorder known to elicit EPS

Study Design• Data collected:

– Age– Gender– Race– Medical and psychiatric diagnoses– Antipsychotic therapy– Anticholinergic therapy– Adverse events

Study Design• Statistical Methods:

– Summary statistics– Comparisons of data across antipsychotic

groups using analysis of variance– Chi-squared analysis– Spearman’s rho– Univariate and multiple logistic regression

analyses

Results235 antipsychotic

trials identified(197 subjects)

179 trials(152 subjects)

Excluded: 29 – not enough info11 – no records > 1 month7 – age4 – dates3 – non-antipsychotic causing EPS2 – other

ResultsCharacteristic ValueAge 14.5 yrs (5 – 18)Gender 77 female, 75 maleRace 110 – African American

28 – Caucasian9 – Hispanic3 – Other2 - Asian

Reported for 152 subjectsFor subjects with > 1 antipsychotic trial, only assessed first trial

Antipsychotic Use: Baseline

27

2716

10

9

54 2

Risperidone

Quetiapine

Aripiprazole

Ziprasidone

PolypharmacyOlanzapine

FGA

Clozapine

% antipsychotic use

Polypharmacy:  > 1 antipsychoticFGA: fluphenazine, chlorpromazine, haloperidol

Psychiatric DiagnosesComorbid Dx:

Other (42)PTSD (39)ADHD (25)Dev (24)MDD (3)

Psych Dx: 2 (1-3)Other Dx: 3 (1-7)

BP = bipolar disorder, MDD = major depressive disorder, Sch = schizophrenia, PTSD = post-traumatic stress disorder, ADHD = attention deficit hyperactivity disorder, Dev = developmental disorder

Anticholinergic Use• Concomitant anticholinergic use with antipsychotic

identified in 32 subjects (21%)– Before start of AP: n=3 (2%)– Simultaneous initiation: n=17 (11.2%)– Within 30 days after AP: n=28 (18.4%)

• Only 12 subjects (8%) with documented EPS • Anticholinergics used:

– Benztropine (n=32)– Diphenhydramine (n=1)

Anticholinergic Use

Anticholinergic Use – 30 DaysVariable

Mean ± SDDifference P value

On AC Not on AC

Age 14.5 ± 2.3 14.5 ± 2.4 0.05 0.92

BMI 27.8 ± 6.5 28.2 ± 6 -0.37 0.78

AP Dose 551 ± 436 384 ± 378 167 0.041

Total # of meds 4.5 ± 2.3 3.5 ± 1.8 1.04 0.0096

# psych diagnoses 2.2 ± 0.7 1.8 ± 0.8 0.36 0.037

# total diagnoses 3.4 ± 1.3 3 ± 1.4 0.34 0.23

Anticholinergic Use

Odds Ratios – Anticholinergic for 30 days (unadjusted)

Variable Odds Ratio 95% CI P value

Age 1.12 (0.13, 11.7) 0.92

Gender (male) 2.56 (2.56, 2.56) 0.03

Total # psych 4.45 (1.06, 19.1) 0.04

Total # dx 2.99 (0.49, 17.9) 0.23

AP Start Class (SGA vs

FGA/poly)14.49 (14.49, 14.49) <0.0001

Start Dose 5.14 (1.07, 24) 0.04Daily Dose 1

mo 4.76 (1, 22.1) 0.009

Odds Ratios – Anticholinergic for 30 days(adjusted)

Variable Odds Ratio 95% CI P value

Gender (male) 1.52 (1.52, 1.52) 0.41

Total # psych 4.72 (0.88, 25.9) 0.07

AP Start Class (SGA vs

FGA/poly)18 (14.49, 14.49) <0.0001

Start Dose 0.14 (0.005, 3.4) 0.24

Daily Dose 1 mo 3.8 (0.24, 51.3) 0.33

Anticholinergic UseDiscussion

• Substantial number of pediatric patients with documented usage of antipsychotics

• Extensive off-label usage of antipsychotics• Majority using SGA vs. conventional

agents• Most commonly used SGA in study

subjects consistent with a priori observations

Discussion• Documented EPS in 8% of subjects• Anticholinergic use documented in 21% of subjects• Anticholinergic started before, after and concurrently

with antipsychotics• Use of anticholinergic at 30 days observed more

frequently in subjects taking risperidone; less commonly in those taking quetiapine; not at all in those taking aripiprazole

• Controlling for confounding variables with multiple logistic regression:– Antipsychotic class = key predictor

Which of the following antipsychotic medications is most likely to requirethe use of anticholinergic therapy to control or prevent EPS in a 15 year old patient with schizophrenia?

A. QuetiapineB. AripiprazoleC. RisperidoneD. All of the above

Limitations• Retrospective study• Lack of documentation

– Short duration of AP therapy– Indications for medications– Specific EPS– Psychiatric history

• Majority of subjects transferred from outside facility• Antipsychotic medications commonly initiated prior

to start date documented in UIC medical records/pharmacy database

• Other

Future Directions• Prospective, randomized controlled

studies needed to assess cause-effect relationship among variables

• Investigate predictors of anticholinergicuse in pediatric patients taking antipsychotics– Gender, psychiatric diagnoses, antipsychotic

class, dose – Genetic predisposition to EPS

Acknowledgements• Jeffrey Bishop, Pharm.D.• Juliana Chan, Pharm.D.• Mark Kliethermes, RPh, MBA

References1. Wonodi I, Reeves G, Carmichael D, et al. Tardive dyskinesia in children treated with atypical antipsychotic medications. Movement Disorders.

2007;22(12):1777-1782.2. Jensen PS, Buitelaar J, Pandina GJ, Binder C, Haas M. Management of psychiatric disorders in children and adolescents with atypical

antipsychotics. Eur Child Adolesc Psychiatry. 2007;16:104-120. 3. Gebhardt S, Hartling F, Hanke M, et al. Relations between movement disorders and psychopathology under predominantly atypical

antipsychotic treatment in adolescent patients with schizophrenia. Eur Child Adolesc Psychiatry. 2008;17:44-53.4. Fleischhaker C, Heiser P, Hennighausen K, et al. Clinical drug monitoring in child and adolescent psychiatry: side effects of atypical

neuroleptics. J Child Adolesc Psychopharmacol. 2006;16(3):308-316. 5. Lewis R. Typical and atypical antipsychotics in adolescent schizophrenia: efficacy, tolerability, and differential sensitivity to extrapyramidal

symptoms. Can J Psychiatry. 1998;43:596-604.6. Sikich L, Hamer RM, Bashford RA, Sheitman BB, Lieberman JA. A pilot study of risperidone, olanzapine, and haloperidol in psychotic youth:

a double-blind, randomized, 8-week trial. Neuropsychopharmacology. 2004;29:133-145. 7. Seeman P. Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002;47:27-38.8. Wood M. Role of the 5-HT2c receptor in atypical antipsychotics: hero or villain? Curr Med Chem. 2005;5:63-66. 9. Thomson MICROMEDEX, editor. Drug information for the health care professional. 27th ed. Greenwood Village: Thomson MICROMEDEX;

2007.10. Harrison-Woolrych M, Garcia-Quiroga J, Ashton J, Herbison P. Safety and usage of atypical antipsychotic medications in children. Drug

Safety. 2007;30(7):569-579. 11. Masi G, Mucci M, Pari C. Children with schizophrenia: clinical picture and pharmacological treatment. CNS Drugs. 2006;20(10):841-866. 12. Lofton AL, Klein-Schwartz W. Atypical experience: a case series of pediatric aripiprazole exposures. Clin Toxicol. 2005;43:151-153. 13. Reynolds CR, Fletcher-Janzen E, eds. Handbook of Clinical Child Neuropsychology 3rd ed. New York, NY: Springer; 2008:577.14. Minzenberg MJ, Poole JH, Benton C, Vinngradov S. Association of anticholinergic load with impairment of complex attention and memory in

schizophrenia. Am J Psychiatry. 2004;161:116-124. 15. McEvoy JP, Freter S. The dose-response relationship for memory impairment by anticholinergic drugs. Comprehensive Psychiatry.

1989;30(2):135-138. 16. Bishop JR, Pavuluri MN. Review of risperidone for the treatment of pediatric and adolescent bipolar disorder and schizophrenia.

Neuropsychiatric Disease and Treatment. 2008;4(1):55-68.17. Riedel M, Spellmann I, Strassnig M, et al. Effects of risperidone and quetiapine on cognition in patients with schizophrenia and

predominantly negative symptoms. Eur Arch Psychiatry Clin Neurosci. 2007;257:360-370.18. Paton C, Duffett R, Harrington M, Lelliott P, Okocha C, Sensky T. Patterns of antipsychotic and anticholinergic prescribing for hospital

inpatients. J Psychopharmacol. 2003;17:223.19. Sanford M, Keating GM. Aripiprazole in adolescents with schizophrenia. Pediatr Drugs 2007;9(6):419-423.

Questions?

Residency Project Pearls – Anticholinergic Use in Children and Adolescents Taking Antipsychotics 

Irene Hong, Pharm.D.  

References: 

1. Wonodi I, Reeves G, Carmichael D, et al. Tardive dyskinesia in children treated with atypical antipsychotic medications. Movement Disorders. 2007;22(12):1777‐1782. 

2. Jensen PS, Buitelaar J, Pandina GJ, Binder C, Haas M. Management of psychiatric disorders in children and adolescents with atypical antipsychotics. Eur Child Adolesc Psychiatry.  2007;16:104‐120.  

3. Gebhardt S, Hartling F, Hanke M, et al. Relations between movement disorders and psychopathology under predominantly atypical antipsychotic treatment in adolescent patients with schizophrenia. Eur Child Adolesc Psychiatry. 2008;17:44‐53. 

4. Fleischhaker C, Heiser P, Hennighausen K, et al. Clinical drug monitoring in child and adolescent psychiatry: side effects of atypical neuroleptics. J Child Adolesc Psychopharmacol. 2006;16(3):308‐316.  

5. Lewis R. Typical and atypical antipsychotics in adolescent schizophrenia: efficacy, tolerability, and differential sensitivity to extrapyramidal symptoms. Can J Psychiatry. 1998;43:596‐604. 

6. Sikich L, Hamer RM, Bashford RA, Sheitman BB, Lieberman JA. A pilot study of risperidone, olanzapine, and haloperidol in psychotic youth: a double‐blind, randomized, 8‐week trial. Neuropsychopharmacology. 2004;29:133‐145.  

7. Seeman P. Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002;47:27‐38. 

8. Wood M. Role of the 5‐HT2c receptor in atypical antipsychotics: hero or villain? Curr Med Chem. 2005;5:63‐66.  

9. Thomson MICROMEDEX, editor. Drug information for the health care professional. 27th ed. Greenwood Village: Thomson MICROMEDEX; 2007. 

10. Harrison‐Woolrych M, Garcia‐Quiroga J, Ashton J, Herbison P. Safety and usage of atypical antipsychotic medications in children. Drug Safety. 2007;30(7):569‐579.  

11. Masi G, Mucci M, Pari C. Children with schizophrenia: clinical picture and pharmacological treatment. CNS Drugs. 2006;20(10):841‐866.  

12. Lofton AL, Klein‐Schwartz W. Atypical experience: a case series of pediatric aripiprazole exposures. Clin Toxicol. 2005;43:151‐153.   

13. Reynolds CR, Fletcher‐Janzen E, eds. Handbook of Clinical Child Neuropsychology  3rd ed. New York, NY: Springer; 2008:577. 

14. Minzenberg MJ, Poole JH, Benton C, Vinngradov S. Association of anticholinergic load with impairment of complex attention and memory in schizophrenia.  Am J Psychiatry. 2004;161:116‐124.  

Residency Project Pearls – Anticholinergic Use in Children and Adolescents Taking Antipsychotics 

Irene Hong, Pharm.D.  

15. McEvoy JP, Freter S. The dose‐response relationship for memory impairment by anticholinergic drugs. Comprehensive Psychiatry. 1989;30(2):135‐138.  

16. Bishop JR, Pavuluri MN. Review of risperidone for the treatment of pediatric and adolescent bipolar disorder and schizophrenia. Neuropsychiatric Disease and Treatment. 2008;4(1):55‐68. 

17. Riedel M, Spellmann I, Strassnig M, et al. Effects of risperidone and quetiapine on cognition in patients with schizophrenia and predominantly negative symptoms. Eur Arch Psychiatry Clin Neurosci. 2007;257:360‐370. 

18. Paton C, Duffett R, Harrington M, Lelliott P, Okocha C, Sensky T. Patterns of antipsychotic and anticholinergic prescribing for hospital inpatients. J Psychopharmacol. 2003;17:223. 

19. Sanford M, Keating GM. Aripiprazole in adolescents with schizophrenia. Pediatr Drugs 2007;9(6):419‐423. 

Residency Project Pearls – Anticholinergic Use in Children and Adolescents Taking Antipsychotics 

Irene Hong 

Post‐test questions 

Which second‐generation antipsychotic(s) is/are FDA‐approved for use in children and adolescents with schizophrenia or bipolar disorder I?  A.Olanzapine B.Risperidone C.Aripiprazole D.B and C E.All of the above  Which of the following antipsychotic‐associated side‐effects are commonly treated with anticholinergic therapy?  A.Weight gain B.Dystonia C.Hyperprolactinemia D. Insulin resistance   

Development and Implementation of a Code Blue Training Program for

Pharmacists: Simulation-Based vs. Traditional Methods

Nadine Lomotan, Pharm.D.September 12, 2009

Speaker Disclosure

The speaker has no conflict of interest to disclose.

Learning Objectives

• Describe the value of having a pharmacist as part of the code blue team

• Identify the most effective method for training pharmacists in code blue emergencies

Advocate Christ Medical Center (ACMC) and Hope Children’s Hospital

• Located in Oak Lawn, IL

• Private, non-profit, 695-bed community teaching hospital

• Level I Trauma Center• 44 full-time staff

pharmacists• 296 code blue

emergencies in 2008

Multidisciplinary Code Team

• Members:– Medical Intensive Cardiac Care Unit

(MICCU) Residents and Interns– Two MICCU nurses– Nursing Manager– Respiratory Therapist– Anesthesia Representative– Chaplain

Audience Poll

How many of you are at an institution where pharmacists respond to code blues?

Of the ones that participate in code blues, how many have used simulation to train your pharmacists?

Background• Pharmacist participation in code blue

events was first reported in the 1970s– As of 2006, only 37% of 1,125 institutions

report that their pharmacists participate on a code team

• Benefits– Lowers mortality rates by 10.5%– Decreases adverse drug reactions by 33%

Bond CA, Raehl CL. Pharmacotherapy 2007;27:481-93.Bond CA, Raehl CL. Pharmacotherapy 2006;26:735-47.

Background• Many methods have been used to train

pharmacists for medical emergencies– Basic Life Support (BLS) and Advanced

Cardiac Life Support (ACLS) certification– Continuing education programs

• No studies evaluating the use of simulation as a training method for pharmacists

Machado C, et al. Hospital Pharmacy. 2003;38(1):40-49.

Background• Use of simulation technology is

expanding in medical education• Simulation places trainees in life-like

situations with immediate feedback• Several studies with medical residents

have demonstrated improved proficiency in their trauma skills using patient simulators

Wayne DB, et al. Teach Learn Med. 2005;17(3):202-208. Wayne DB, et al. J Gen Intern Med. 2006;21:251-256.Wayne DB, et al. Chest. 2008;133:56-61.

ACMC’s Simulation Learning Center• Opened in August 2008• Contains 3 hospital beds, medical equipment

and 5 life-sized mannequins specially designed for medical training

ACMC’s Simulation Learning Center

• Features of patient simulator:– Palpable pulse– Audible heart and breath sounds– Mouth speaker with patient responses

• Active telemetry monitors display real-time EKG rhythms, blood pressure, and oxygen saturation

ACMC’s Simulation Learning Center

Study Objective

• To determine the effectiveness of a simulation-based code blue training program for pharmacists compared to a traditional training method in a classroom environment

Methods• Prospective, pre- and post-test design

– Primary measurements obtained at baseline and after the educational intervention

• IRB exempt• Inclusion criteria

– Must be a pharmacist currently employed at ACMC

• Exclusion criteria– Previous ACLS training– Previous experience in responding to code

blues

BLS, ACLS & Pharmacology Lecture

(n = 6)

Baseline Exam & Survey

Classroom(n = 3)

Simulation Lab(n = 3)

Case #1 Case #1

Case #2 Case #2

Case #3 Case #3

Final Assessment Exam & Survey

Methods

• Primary Outcome– Change in mean written test and survey scores

• Secondary Outcome– Comparison of oral competency exam scores

Training Program• All study participants

completed the American Heart Association (AHA)-approved BLS course

• Time Requirement = 4 hours classroom instruction

Training Program

• All study participants completed the AHA-approved ACLS course

• Time Requirement = 14 hours classroom instruction

Training Program• ACLS Pharmacology Lecture

– 1 hour– Attended by all study participants – Review of indications, appropriate dosing,

and side effects of each resuscitation medication

Training Program• Written baseline test

– Completed by all study participants prior to randomization

– Time allotted: 30 minutes– 17 questions

• Multiple-choice, true/false, fill-in-the-blank– Content

• Dosing, indications, administration, case-based

Training Program• Survey (18 questions)

– Completed by all study participants prior to randomization

– Evaluating comfort level with various resuscitation tasks

– 5-point Likert scale• 1 = Very uncomfortable to 5 = Very comfortable• Maximum score of 90

Training Program• Participants then randomized to train in either

a simulation lab or classroom setting– Randomization via online software

(www.randomization.com)– Practice 3 scenarios

• Case 1 = Pulseless arrhythmias (asystole, pulseless electrical activity, ventricular fibrillation/tachycardia)

• Case 2 = Bradycardia• Case 3 = Supraventricular tachycardia

– Facilitated by same instructors

Training Program• Simulation Group

– Patient simulator programmed to mimic the 3 case scenarios

– All 3 participants worked together during the cases

– Participants were required to read EKG rhythms using monitors

– Participants were able to practice preparing medications

Training Program

• Traditional Group– Classroom setting– All 3 participants worked together during the

cases– Electrocardiographic paper strips were used– ED pharmacist verbally moderated changes in

vital signs or physical exam– Participants also able to practice preparing

medications

Training Program• Oral competency exams

– Both groups were tested during each case to check adherence to ACLS guidelines

– Scoring system• 0 = not done/done incorrectly • 1 = done correctly

– Case 1: maximum score of 13– Case 2: maximum score of 4– Case 3: maximum score of 6

• At completion, participants completed the same written assessment exam and survey

Baseline Demographic Data(n = 6)

Characteristic Simulation Group (n=3)

Traditional Group (n=3)

Mean Age, y (Range)

36 (25-57) 46 (26-59)

Male (%) 1 (33) 2 (67)

Female (%) 2 (67) 1 (33)

Mean pharmacy experience, y

(Range)

11.7 (1-32) 23.3 (4-36)

Written Assessment Exam Results(Maximum score = 17)

10

13.7 14.3 14

0

2

4

6

8

10

12

14

16

Mea

n Te

st S

core

s

Baseline Final

Simulation

Traditional

Comfort Level Survey Results(Maximum score = 90)

64

56

6865

0

10

20

30

40

50

60

70

Mea

n To

tal S

core

s

Baseline Final

Simulation

Traditional

Oral Competency Exam Results

77 75

100

85

100 100

0102030405060708090

100

% S

core

Simulation Traditional

Case 1Case 2Case 3

Conclusions• Traditional group performed better

overall during intervention– Also with a greater increase in comfort

level• Simulation group had greatest

improvement in mean written test scores

• Need larger sample size to determine significance and full effect of study

Limitations• Small sample size

– Scheduling conflicts and lack of pharmacy coverage

– Budget issues• No statistics due to sample size• Recall bias• Lack of familiarity with simulation• Confounding variable: years of

experience

Future Directions• An additional 18 pharmacists will be

enrolled in the study • Goal is to have all pharmacists trained • Implementation of pharmacists as

members of code blue team• Continued training and performance

reviews• Publication of study

Special Thanks To…

• Rolla Sweis, Pharm.D., M.A.– ED Clinical Coordinator

• Daniel Girzadas, M.D.– ED Director of Simulation Learning Center

Question• What is the approximate percentage of

hospitals nation-wide that have pharmacists as part of their code blue team?A. 50%B. 70%C. 35%D. 15%

Question• A key difference between training in a

simulated environment versus in a classroom is that:

A. Simulation provides more interaction with a moderator than in the classroom.

B. New skills can only be taught in the classroom.

C. Simulation improves knowledge retention better than in a classroom.

D. All of the above.

Questions?

Nadine Lomotan 121-000-09-045-L01P Post-Test Questions:

1. True/False. Studies have shown that pharmacist participation in code blue emergencies reduce adverse drug reactions and improve hospital mortality rates.

2. What are some barriers to incorporating pharmacists as part of the code blue team?

The Impact of Pharmacist Intervention on Stress Ulcer

ProphylaxisJenny Niemerg, Pharm.D.

Clinical Assistant ProfessorSIUE School of Pharmacy

Speaker has no conflict of interest

Objectives• Recognize risk factors for developing

stress-related mucosal disease (SRMD).

• Determine the appropriate length of therapy for stress ulcer prevention.

CaseJD is a 50 y/o AAM who has been on a ventilator in the SICU for 5 days since he was successfully resuscitated after going into cardiac arrest during a CABG procedure. You’re looking over the medication list and notice the patient is receiving a simplified lansoprazole suspension.

CaseLabs:

AST 29, ALT 17, Alk P. 42INR 0.9Chest X-ray: left lower lobe infiltrate

1403.8

10025

110.9 122

13.215.0 188

36.1

CaseWhat risk factor for SRMD does this patient have?

A. Mechanical ventilation >48 hoursB. PneumoniaC.Myocardial infarctionD.Acute renal failure

Therapeutic Guidelines on Stress Ulcer Prophylaxis

• American Society of Health-System Pharmacists (ASHP)• Focus on intensive care unit patients• Not recommended for non-ICU patients• Reasonable to treat non-ICU patients with >1 risk factor

ASHP. Am J Health-Syst Pharm.1999;56:347-79.

Major Risk Factors• Independent risk factors

– Mechanical ventilation >48h– Coagulopathy (PLT <50,000, or INR >1.5)

ASHP. Am J Health-Syst Pharm. 1999;56:347-79.

Major Risk Factors• Acute renal failure• Acute hepatic failure• Severe head injury• Thermal injury of >35% BSA

• Major trauma• Spinal cord injury• Major surgery (lasting >4 h)• History of GI ulceration or

bleeding within 1 year

ASHP. Am J Health-Syst Pharm. 1999;56:347-79.

Minor Risk Factors>2 of the following• ICU stay >1 week• Occult bleeding lasting >6 days• High dose corticosteroids

– (>250mg hydrocortisone or equivalent)• Sepsis

ASHP. Am J Health-Syst Pharm. 1999;56:347-79.

CaseWhat risk factor for SRMD does this patient have?

A. Mechanical ventilation >48 hoursB. PneumoniaC.Myocardial infarctionD.Acute renal failure

Pharmacologic Therapy

Contraindications

Potential Complications• Inappropriate

continuation of therapy• ADR• Dosing adjustments

• Drug interactions• Duplication of therapy• Polypharmacy• Cost

No absolute contraindication to short-term prophylaxis

ASHP. Am J Health-Syst Pharm. 1999;56:347-79

Potential Complications• Nosocomial pneumonia• Community-acquired pneumonia (CAP)• Clostridium difficile colitis• Bone fractures

Cunningham R, et al. J Hosp Infect. 2003; 54:243-5.Dial S, et al. JAMA. 2005; 294:2989-95.

Lowe DO. Clin Infect Dis. 2006; 43:1272-6.Maton PN. Aliment Pharmacol Ther. 2005; 22:45-52.

Yang YX, et al. JAMA. 2006; 296:2947-53.

CaseOne week later, the same patient has improved and has been extubated. What is the next step regarding SUP?

A. Change lansoprazole to famotidineB. Lansoprazole should be discontinued because he no

longer has risk factors for SRMDC.SUP should be continued for 4 weeksD.SUP should be continued until discharge

Appropriate use of stress ulcer prophylaxis in general medicine patients• Primary Objective: To compare the appropriate use of

SUP in general medicine patients before and after physician education

• Secondary Objective: To determine how many patients receiving SUP receive AST upon discharge

• Retrospective medication use evaluation of AST for SUP

Subjects

Inclusion criteria Exclusion criteriaAge >18 years Continuation of AST taken

prior to admissionAdmission to general

internal medicine teaching service

Condition requiring AST

AST administered during hospital stay

Methods• Data collection

– Pyxis reports from general medicine floors• One month period before and after intervention• Famotidine (tabs or inj.) or omeprazole (caps)

– Paper and electronic charts• Criteria for stress ulcer risk

– Major and minor risk factors adapted from ASHP guidelines

Methods• Educational intervention

– Pharmacist delivered didactic lecture– Summary of ASHP therapeutic guidelines on SUP– Literature review– Epidemiology, pathophysiology, risk factors, prevention– Potential complications of AST

Methods• E-mailed summary of lecture• Laminated pocket card• Statistical Analysis

– Chi-square test– α = 0.05

Comparison of SUPBefore and After Intervention

Control(n = 122)

Intervention(n = 54)

Received AST for SUP 72 16

Met criteria for SUP 10 6

Comparison of SUPBefore and After Intervention

SUP Continued Upon Discharge

Control(n = 72)

Intervention(n = 16)

Discharged on AST 11 (15%) 5 (31%)

Limitations• Study design• Charting• No long-term follow-up• Education provided to medical residents only• Individual resident variability• Generalizability

Conclusions• Pharmacist intervention improved appropriate use of

SUP in non-ICU patients• Expand role of pharmacist-driven education• Discharge counseling• Target misuse of other medications

The Impact of Pharmacist Intervention on Stress Ulcer Prophylaxis

Jenny Niemerg, Pharm.D. Clinical Assistant Professor SIUE School of Pharmacy

Learning Objectives 1. Recognize risk factors for stress-related mucosal disease 2. Determine the appropriate length of therapy for stress ulcer prevention Patient Case 1. JD is a 50 y/o AAM who has been on a ventilator in the SICU for 5 days since he was successfully resuscitated after going into cardiac arrest during a CABG procedure. You’re looking over the medication list and notice the patient is receiving a simplified lansoprazole suspension. Labs: BUN 11, S.Cr. 0.9, AST 29, ALT 17, INR 0.9, WBC 15.0, Hgb 13.2, Hct 36.1, PLT 188 Chest X-ray: left lower lobe infiltrate What risk factor for SRMD does this patient have? A. Mechanical ventilation >48 hours B. Pneumonia C. Myocardial infarction D. Acute renal failure 2. One week later, the same patient has improved and has been extubated. What is the next step regarding SUP? A. Change lansoprazole to famotidine B. Lansoprazole should be discontinued because he no longer has risk factors for SRMD C. SUP should be continued for 4 weeks D. SUP should be continued until discharge

I. Therapeutic Guidelines on Stress Ulcer Prophylaxis (SUP)1 A. American Society of Health-System Pharmacists (ASHP) B. Focus on intensive care unit patients C. Not recommended for non-ICU patients D. Reasonable to treat non-ICU patients with >1 risk factor

II. Risk Factors1

A. Major Risk Factors Independent risk factors 1. Mechanical ventilation >48h 2. Coagulopathy

a. PLT <50,000 b. INR >1.5

3. Acute renal failure 4. Acute hepatic failure 5. Severe head injury 6. Thermal injury of >35% BSA 7. Major trauma 8. Spinal cord injury 9. Major surgery (lasting >4 h) 10. History of GI ulceration or bleeding within 1 year

B. Minor Risk Factors: >2 of the following

2  

1. ICU stay >1 week 2. Occult bleeding lasting >6 days 3. High dose corticosteroids (>250mg hydrocortisone or equivalent) 4. Sepsis

III. Therapy Options1,2,3,4,5

A. Volume and hemodynamic support B. Enteral nutrition C. Gastroprotective Agents

1. Antacids 2. Sucralfate

D. Acid Suppressive Therapy 1. H2 Receptor Antagonists 2. Proton Pump Inhibitors

IV. Contraindications1

A. No absolute contraindications to short-term use of prophylaxis medications B. Potential complications

1. Side effects 2. Dosing adjustments 3. Polypharmacy 4. Cost 5. Inappropriate continuation of therapy after discharge 6. Duplication of therapy

V. Complications6,7,8,9,10,11,12

A. Nosocomial pneumonia B. Community-acquired pneumonia (CAP) C. Clostridium difficile colitis D. Bone fractures

VI. Pharmacist Intervention

Title Appropriate use of stress ulcer prophylaxis in general medicine patients

Study Design Retrospective medication use evaluation (MUE) Hypothesis Physician education will decrease the frequency of inappropriate SUP Outcomes Number of patients receiving appropriate AST for SUP Methods • Inclusion: Age >18 years, admission to general internal medicine teaching

service, AST administered during hospital stay • Exclusion: Continuation of AST taken prior to admission, health condition

requiring AST (GERD, PUD, gastrointestinal bleeding, etc.) • Data collection

-Pyxis reports of famotidine tablets or injection, or omeprazole capsules administered to any patient on general medicine floors for one month before and after physician education -Paper and electronic charts

• Criteria for stress ulcer risk -Major Risk Factors: mechanical ventilation >48h, coagulopathy, PLT <50,000, INR >1.5, acute renal failure, acute hepatic failure, severe head injury, thermal injury of >35% BSA, major trauma, spinal cord injury, major surgery (lasting >4 hours), history of GI ulceration or bleeding within 1 year

-Minor Risk Factors- >2 of the following: ICU stay >1 week, occult bleeding lasting >6 days, high dose corticosteroids (>250mg hydrocortisone or equivalent), sepsis • Educational intervention

-Pharmacist delivered didactic lecture on stress ulcers: ASHP therapeutic

3  

guidelines on stress ulcer prophylaxis, literature review, epidemiology, pathophysiology, risk factors, prophylactic treatment, complications of AST -E-mailed summary of the lecture -Pocket card distributed to all medical residents

Statistical Analysis • α = 0.05 • Chi-square test

Results • Figure 1 • Prior to intervention

-72 patients received AST for SUP -10 patients (13.9%) met criteria for SUP -11 patients (15%) discharged on AST

• Post-intervention -16 patients received AST for SUP -6 patients (37.5%) met criteria for SUP -5 patients (31%) discharged on AST

Limitations • Study design • Charting • No long-term follow-up • Education provided to medical residents only • Individual resident variability • Generalizability

Conclusions • Pharmacist intervention improved appropriate use of SUP in non-ICU patients Figure 1: Percentage of general medicine patients receiving SUP

VII. Conclusions A. Pharmacist intervention improved appropriate use of SUP in non-ICU patients B. Expand role of pharmacist-driven education C. Discharge counseling D. Target misuse of other medications

4  

References 1. ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. Am J Health-Syst Pharm. 1999; 56:347-

79. 2. Martindale RG. Contemporary strategies for the prevention of stress-related mucosal bleeding. Am J

Health-Syst Pharm. 2005; 62(Suppl 2):S11-7. 3. Cook DJ, Witt LG, Cook RJ, Guyatt GH. Stress ulcer prophylaxis in the critically ill: a meta-analysis.

Am J Med. 1991; 91:519-27. 4. Cook D, Guyatt G, Marshall J, et al. A comparison of sucralfate and ranitidine for the prevention of

upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. N Engl J Med. 1998; 338:791-7.

5. Conrad SA, Gabrielli A, Margolis B, et al. Randomized, double-blind comparison of immediate-release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients. Crit Care Med. 2005; 33:760-5.

6. Cunningham R, Dale B, Undy B, Gaunt N. Proton pump inhibitors as a risk factor for Clostridium difficile diarrhea. J Hosp Infect. 2003; 54:243-5.

7. Dial S, Alrasadi K, Manoukian C, Huang A, Menzies D. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA. 2005; 294:2989-95.

8. Lowe DO, Mamdani MM, Kopp A, et al. Proton pump inhibitors and hospitalization for Clostridium difficile-associated disease: a population-based study. Clin Infect Dis. 2006; 43:1272-6.

9. Maton PN. Review article: prevention of stress-related mucosal bleeding with proton-pump inhibitors. Aliment Pharmacol Ther. 2005; 22(Suppl. 3):45-52.

10. Laheij RJ, Sturkenboom MC, Hassing RJ, Dieleman J, Stricker BH, Jansen JB. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA. 2004;292:1955-60.

11. Sarkar M, Hennessy S, Yang Y. Proton-pump inhibitor use and the risk for community-acquired pneumonia. Annals of Internal Medicine. 2008;149:391-98.

12. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296:2947-53.

 

Post-test Questions J. Niemerg 09-045 1. Which of the following are the 2 independent major risk factors for stress ulcers?

a. Thermal injuries over >35% of BSA and ICU stay >7 days b. Major surgery and occult bleeding lasting 6 days c. High dosage corticosteroids and sepsis d. Mechanical ventilation lasting >48 hours and coagulopathy

2. How long should a patient receive stress ulcer prophylaxis?

a. 3 months after the patient no longer has a risk factor b. Lifetime c. Once risk factors are no longer present, stress ulcer prophylaxis should be discontinued d. 3 days